Urinary intermediates of tryptophan as indicators of the gut microbial metabolism

Urinary intermediates of tryptophan as indicators of the gut microbial metabolism
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色氨酸的尿液中间产物作为肠道微生物代谢的指标

DOI:
10.1016/j.aca.2017.08.022
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发表时间:
2017-09-22
影响因子:
6.2
通讯作者:
Spacil, Zdenek
Spacil, Zdenek
中科院分区:
化学1区
文献类型:
--
作者:
Pavlova, Tereza;Vidova, Veronika;Spacil, Zdenek

文献摘要

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虽然超过10%的人类代谢组与肠道微生物代谢直接相关,但特定的代谢物在很大程度上没有被表征。因此,为了阐明宿主-微生物群相互作用的分子基础,鉴定和定量生物体液(如尿液或血浆)中微生物群相关代谢产物的方法是必要的。在本研究中,我们重点研究了色氨酸代谢,采用超高效液相色谱(UHPLC)和串联质谱法进行定量分析,特别是选择反应监测(SRM)。基于HMDB分类,利用代谢物标准物生成16个色氨酸代谢中间体的SRM文库,这些中间体既有人类内源的,也有微生物相关的。接下来,SRM测定被用于筛选产妇尿液样本和新生儿的干燥尿液样本。该方法在尿液样本中发现了微生物相关代谢物(甲基吲哚-3-乙酸酯和甲基吲哚-3-丙酸酯),并对8种色氨酸代谢中间体进行了定量分析。据我们所知,这项研究首次尝试用UHPLC-SRM方法探索以前未报道的尿液中微生物代谢物,并同时测定微生物调节色氨酸代谢成分的新方法。(C) 2017 Elsevier B.V.版权所有
While over 10% of the human metabolome is directly associated with the gut microbial metabolism, specific metabolites are largely uncharacterized. Therefore, methods for the identification and quantification of microbiota-associated metabolites in biological fluids such as urine or plasma are necessary in order to elucidate the molecular basis of host-microbiota interaction. In this study, we focused on the tryptophan metabolism, employing quantitative assays by ultra-high performance liquid chromatography (UHPLC) and tandem mass spectrometry, specifically selected reaction monitoring (SRM). Metabolite standards were utilized to generate SRM library for 16 intermediates of the tryptophan metabolism which were human endogenous as well as microbiota-associated based on the HMDB classification. Next, the SRM assays were utilized for screening in maternal urine samples and in dried urine specimens from neonates. The approach resulted in the discovery of microbiota-associated metabolites (methyl indole-3-acetate and methyl indol-3-propionate) previously unreported in urine samples and additionally in quantification of 8 intermediates of the tryptophan metabolism. To the best of our knowledge, this study represents the first attempt to explore previously unreported microbial metabolites in urine by UHPLC-SRM and novel methodology for simultaneous determination of microbiota-modulated component of Trp metabolism. (C) 2017 Elsevier B.V. All rights reserved.